TY - JOUR
T1 - Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas
AU - Kim, Sang Geol
AU - On-On Chan, Annie
AU - Wu, Tsung Teh
AU - Issa, Jean Pierre J.
AU - Hamilton, Stanley R.
AU - Rashid, Asif
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Background & Aims: Carcinomas of the extrahepatic bile ducts, ampulla of Vater, and duodenum are uncommon, and their epigenetic and genetic alterations are not well characterized. Methods: We therefore compared the methylation profile and genetic alterations in 18 extrahepatic biliary, 9 ampullary, and 12 duodenal carcinomas. We evaluated methylation at p16, p14, and human Mut L homologue (hMLH1) by methylation-specific PCR (MSP), and at cyclooxygenase 2 (COX2), O6-methylguanine methyltransferase (MGMT), estrogen receptor (ER), retinoic acid receptor β2 (RARβ), and T-type calcium channel (CACNA1G) genes, and methylated in tumor 1 (MINT1), MINT2, MINT25, MINT27, and MINT31 loci by combined bisulfite restriction analysis (COBRA); mutation of K-ras, p53, p16, and p14 genes by sequencing; loss of heterozygosity of chromosome 9p; and microsatellite instability (MSI). Results: Duodenal carcinomas were methylated more frequently or had increased methylation densities than biliary carcinomas at p14 (P = 0.04), hMLH1 (P = 0.04), MGMT (P = 0.01), MINT1 (P = 0.01), MINT25 (P = 0.01), MINT27 (P = 0.001), RARβ (P = 0.03), and ER (P = 0.001), and than ampullary carcinomas at RARβ (P = 0.02) and ER (P = 0.03). In contrast, the methylation profiles of biliary and ampullary carcinomas were not statistically different. Simultaneous methylation of 3 or more CpG islands (CpG island methylator phenotype-high) was more common in duodenal cancers (P = 0.004). MGMT methylation was associated with G-to-A mutation in K-ras (P = 0.006), and hMLH1 methylation was associated with MSI-high (P = 0.01). Conclusions: Our findings indicate that the methylation profile and genetic alterations of duodenal carcinomas are distinct from biliary and ampullary carcinomas, and that tumor-specific methylation is associated with gene mutation and MSI.
AB - Background & Aims: Carcinomas of the extrahepatic bile ducts, ampulla of Vater, and duodenum are uncommon, and their epigenetic and genetic alterations are not well characterized. Methods: We therefore compared the methylation profile and genetic alterations in 18 extrahepatic biliary, 9 ampullary, and 12 duodenal carcinomas. We evaluated methylation at p16, p14, and human Mut L homologue (hMLH1) by methylation-specific PCR (MSP), and at cyclooxygenase 2 (COX2), O6-methylguanine methyltransferase (MGMT), estrogen receptor (ER), retinoic acid receptor β2 (RARβ), and T-type calcium channel (CACNA1G) genes, and methylated in tumor 1 (MINT1), MINT2, MINT25, MINT27, and MINT31 loci by combined bisulfite restriction analysis (COBRA); mutation of K-ras, p53, p16, and p14 genes by sequencing; loss of heterozygosity of chromosome 9p; and microsatellite instability (MSI). Results: Duodenal carcinomas were methylated more frequently or had increased methylation densities than biliary carcinomas at p14 (P = 0.04), hMLH1 (P = 0.04), MGMT (P = 0.01), MINT1 (P = 0.01), MINT25 (P = 0.01), MINT27 (P = 0.001), RARβ (P = 0.03), and ER (P = 0.001), and than ampullary carcinomas at RARβ (P = 0.02) and ER (P = 0.03). In contrast, the methylation profiles of biliary and ampullary carcinomas were not statistically different. Simultaneous methylation of 3 or more CpG islands (CpG island methylator phenotype-high) was more common in duodenal cancers (P = 0.004). MGMT methylation was associated with G-to-A mutation in K-ras (P = 0.006), and hMLH1 methylation was associated with MSI-high (P = 0.01). Conclusions: Our findings indicate that the methylation profile and genetic alterations of duodenal carcinomas are distinct from biliary and ampullary carcinomas, and that tumor-specific methylation is associated with gene mutation and MSI.
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U2 - 10.1016/S0016-5085(03)00278-6
DO - 10.1016/S0016-5085(03)00278-6
M3 - Article
C2 - 12730870
AN - SCOPUS:0038638906
SN - 0016-5085
VL - 124
SP - 1300
EP - 1310
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -